Many antibiotics are already known, but new antibiotic substances are still demanded to be provided as a pharmaceutical agent. Compounds which are already known and similar in their structural feature of the molecule to the new antifungal and antiviral antibiotic, benanomicin A 4"'-O-sulfate or a salt thereof now newly provided by the present inventors include benanomicin A, benanomicin B and dexylosylbenanomicin B (see Japanese patent applications Nos. 277,692/87 and 327,163/87 as laid-open under Japanese patent application publications "Kokai" No. 121,293/83 published on 12 May, 1989 and "Kokai" No. 168,694/89 published on 4 July 1989, respectively, as well as their corresponding European patent application publication No. 0 315 147 A2 published on 10 May 1989 and corresponding U.S. patent application Ser No. 264,888 filed on 31 October 1988) as well as pradimicins A, B and C [Oki et al: "Journal of Antibiotics" 41, 1701-1704 (1988); Tsunakawa et al: "J. Org. Chem." 54, 2532-2536 (1989)].
Hitherto, a variety of antibiotics which are produced by microorganisms are already known. Among the known antibiotics, however, such antifungal antibiotics which can exhibit excellent antifungal effects but a low toxicity to mammals are only few. Accordingly, there is always a demand for discovery and exploitation of a new anti-fungal antibiotic which is useful in the therapeutic treatment of various fungal infections in a mammalian animal, including human.
On the other hand, acquired human immunodeficiency syndrome (sometime called merely as "AIDS") has been found to be a disease which is caused due to human T-cells being infected by a causative virus in human blood. The virus which is causative of the acquired human immunodeficiency syndrome is usually termed as acquired human immunodeficiency syndrome virus which is often abbreviated as HIV. It has been reported that certain known compounds have an antiviral activity against HIV. However, any of these compounds having an antiviral activity against HIV is not necessarily satisfactory as a useful remedial agent for AIDS, and there is a strong outstanding demand to develope and provide such a new drug which shows a low toxicity and a high solubility in water, which can show a high activity to inactivate HIV and which are expectable as a useful medicinal agent for therapeutically or preventively treating AIDS.
According to some inventions which are earlier made by the present inventors, there are provided two antibiotics, benanomicin A and benanomicin B, which each have an antifungal activity and an HIV-inactivating activity, as well as a process for the production of benanomicins A and B by cultivation of an actinomycete strain MH193-16F4 (see the above-mentioned European patent application publication No. 0 315 147 A2 and its corresponding U.S. patent application Ser No. 264,888). Furthermore, there is provided a pharmaceutical composition for inactivating HIV virus, which comprises benanomicin A or benanomicin B as active ingredient (see Japanese patent application publication "Kokai" No. 56,432/90, published 26 February 1990 and its corresponding European patent application No. 89.402315.9 filed on 21 August 1989 and corresponding U.S. patent application Ser No. 394,539 filed on 16 August 1989. The chemical structure of benanomicin A is shown by the following formula (II) ##STR2## As another derivatives of benanomicins A and B, there are also earlier provided dexylosylbenanomicin A (Japanese patent application No. 248,143/89 filed on Sept. 26, 1989) and N-acetylbenanomicin B (Japanese patent application No. 4701/89, filed on Jan. 13, 1989 and its corresponding U.S. patent application Ser. No. 459,352 and corresponding European patent application No. 0.100210.5). However, benanomicins A and B, dexylosylbenanomicins A and B, as well as N-acetylbenanomicin B which are earlier provided by us in the above-mentioned earlier patent applications do not have a satisfactorily high solubility in water and, due to this, their therapeutic uses are limited to an extent. In this situation, we, the present inventors, have made researches in an attempt to provide such new derivatives of benanomicins A and B which have both the desirable antifungal activity and antiviral activity and additionally can show an improved solubility in water, as compared with the parent benanomicins A and B. As a result, we have now found that when the hydroxyl group at 4"'-position of benanomicin A is chemically converted into its sulfate ester derivative, there can be produced a new antibiotic, benanomicin A 4"'-O-sulfate or a salt thereof, which has an improved water-solubility over that of the parent benanomicin A and exhibits a useful antifungal activity and antiviral activity. We have studied the physicochemical and biological properties of benanomicin A 4"'-O-sulfate or its salts to confirm that benanomicin A 4"'-O-sulfate and a salt thereof are new substance clearly distinguishable from any of the known antibiotics. Thus, we have acomplished this invention.
Thus, an object of this invention is to provide a new antibiotic, benanomicin A 4"'-O-sulfate or a salt thereof which exhibits an antifungal activity and an antiviral activity as well as an improved solubility in water. Another object of this invention is to provide a process for the production of the new antibiotic, benanomicin A 4"'-O-sulfate and a salt thereof. Further objects of this invention will be clear from the following descriptions.